Vitamin C Alleviates BPA Embryotoxicity by Attenuating Oxidative Stress and DNA Damage-Mediated Apoptosis via Modulation of the ATM/Chk2/p53 Pathway

Bisphenol A (BPA), an environmental contaminant that migrates from food packaging, poses significant risks to embryonic development. This study investigated the protective effects and mechanisms of vitamin C (l-ascorbic acid) against BPA-induced embryotoxicity using <i>Xenopus laevis</i> embryos and P19 stem cells under a simultaneous exposure design. A multiassay approach was applied, including developmental bioassays, histological analysis, single-cell gel electrophoresis, and molecular profiling. The results showed that vitamin C significantly alleviated BPA-induced mortality, malformations, growth retardation, neurodevelopmental impairments, and notochord damage. Mechanistically, vitamin C restored the expression of antioxidant genes (<i>gpx4</i>, <i>sod</i>, <i>ppard</i>, and <i>cat.2</i>), reduced reactive oxygen species generation and oxidative DNA damage, and suppressed apoptosis via modulation of the ATM/Chk2/p53 signaling pathway. These findings demonstrate that vitamin C mitigates BPA-induced embryotoxicity by limiting oxidative stress and DNA damage-mediated apoptosis under coexposure conditions, supporting further evaluation of antioxidant-based protection across different exposure regimens and in combination with other antioxidants.